Saccharopolyspora erythraea’sgenome is organised in high-order transcriptional regions mediated by targeted degradation at the metabolic switch

Marcellin, Esteban; Mercer, Tim R.; Licona-Cassani, Cuauhtémoc; Palfreyman, Robin W.; Dinger, Marcel E.; Steen, Jennifer A.; Mattick, John S.; Nielsen, Lars K.

doi:10.1186/1471-2164-14-15

Cited by 31 publications

(48 citation statements)

References 50 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Saccharopolyspora erythraea is a significant industrial producer of broad-spectrum macrolide antibiotic erythromycin. In recent years, many efforts have been made to explore the mechanism of high-yield erythromycin producer (Carata et al 2009;Marcellin et al 2013;Li et al 2013). One of these mechanisms may include the two-component system (TCS), which is one of the most important signal transduction systems in Streptomyces.…”

Section: Discussionmentioning

confidence: 99%

A two-component system gene SACE_0101 regulates copper homeostasis in Saccharopolyspora erythraea

Qiao

et al. 2020

Bioresour. Bioprocess.

View full text Add to dashboard Cite

Background: Saccharopolyspora erythraea (S. erythraea) is a Gram-positive bacterium widely used for the production of erythromycin, a potent macrolide antibiotic. However, the mechanism behind erythromycin production is poorly understood. In the high erythromycin-producer strain S. erythraea HL3168 E3, the level of copper ions positively correlates with erythromycin production. To explain this correlation, we performed a genome-based comparison between the wild-type strain NRRL23338 and the mutant strain HL3168 E3, and further characterized the identified gene(s) by targeted genome editing, mRNA transcript analysis, and functional analysis. Results:The response regulator of the two-component system (TCS) encoded by the gene SACE_0101 in S. erythraea showed high similarity with CopR of TCS CopRS in Streptomyces coelicolor, which is involved in the regulation of copper metabolism. The deletion of SACE_0101 was beneficial for erythromycin synthesis most likely by causing changes in the intracellular copper homeostasis, leading to enhanced erythromycin production. In addition, Cu 2+ supplementation and gene expression analysis suggested that SACE_0101 may be involved in the regulation of copper homeostasis and erythromycin production. Conclusions:The mutation of SACE_0101 gene increased the yield of erythromycin, especially upon the addition of copper ions. Therefore, the two-component system gene SACE_0101 plays a crucial role in regulating copper homeostasis and erythromycin synthesis in S. erythraea.

show abstract

Section: Discussionmentioning

confidence: 99%

A two-component system gene SACE_0101 regulates copper homeostasis in Saccharopolyspora erythraea

Qiao

et al. 2020

Bioresour. Bioprocess.

View full text Add to dashboard Cite

show abstract

“…These ribosomal subpopulations selectively translate specific subsets of mRNAs, thus regulating translation (62). Evidence of ribosomal subpopulations in actinomycetes has been reported for S. erythraea (20) and S. coelicolor (63)(64)(65), in which rRNA and ribosomal protein operons are differentially expressed and undergo targeted degradation. The results presented here suggest that ribosomal subpopulations might exist in S. erythraea, regulating gene expression at the translational level.…”

Section: Hypothetical Proteinsmentioning

confidence: 99%

“…Targeted RNA degradation has been suggested as a global post-transcriptional mechanism for regulating the developmental cycle and antibiotic production in S. erythraea (20) and S. coelicolor (55). RNase catalysis regulated by phosphorylation has been reported in eukaryotic systems (56) and E. coli for the RNase catalytic domain of the polynucleotide phosphorylase (57).…”

Section: Hypothetical Proteinsmentioning

confidence: 99%

“…The production of secondary metabolites occurs after a critical culture transition known as the "metabolic switch" (19), believed to be triggered by nutrient limitation or oxidative stress. Understanding the regulatory mechanisms underpinning the reorganization of the metabolic and cellular machinery at the metabolic switch (20) is of both fundamental and practical importance, as efficient induction is essential for high-level production. Although some cellular regulatory mechanisms have been explained with regard to transcription (19,20), in vivo protein phosphorylation has not been yet explored at the global level and promises to fill an important gap in the understanding of the biology of actinomycetes.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Temporal Dynamics of the Saccharopolyspora erythraea Phosphoproteome

Licona-Cassani

Lim

Marcellin

et al. 2014

Molecular & Cellular Proteomics

Self Cite

View full text Add to dashboard Cite

Actinomycetes undergo a dramatic reorganization of metabolic and cellular machinery during a brief period of growth arrest ("metabolic switch") preceding mycelia differentiation and the onset of secondary metabolite biosynthesis. This study explores the role of phosphorylation in coordinating the metabolic switch in the industrial actinomycete Saccharopolyspora erythraea. A total of 109 phosphopeptides from 88 proteins were detected across a 150-h fermentation using open-profile two-dimensional LC-MS proteomics and TiO 2 enrichment. Quantitative analysis of the phosphopeptides and their unphosphorylated cognates was possible for 20 pairs that also displayed constant total protein expression. Enzymes from central carbon metabolism such as putative acetyl-coenzyme A carboxylase, isocitrate lyase, and 2-oxoglutarate dehydrogenase changed dramatically in the degree of phosphorylation during the stationary phase, suggesting metabolic rearrangement for the reutilization of substrates and the production of polyketide precursors. In addition, an enzyme involved in cellular response to environmental stress, trypsin-like serine protease (SACE_6340/NC_009142_6216), decreased in phosphorylation during the growth arrest stage. More important, enzymes related to the regulation of protein synthesis underwent rapid phosphorylation changes during this stage. Whereas the degree of phosphorylation of ribonuclease Rne/Rng (SACE_1406/NC_009142_1388) increased during the metabolic switch, that of two ribosomal proteins, S6 (SACE_7351/NC_009142_7233) and S32 (SACE_ 6101/NC_009142_5981), dramatically decreased during this stage of the fermentation, supporting the hypothesis that ribosome subpopulations differentially regulate translation before and after the metabolic switch. Overall, we show the great potential of phosphoproteomic studies to explain microbial physiology and specifically provide evidence of dynamic protein phosphorylation events across the developmental cycle of actinomycetes. Molecular & Cellular

show abstract

“…Examples of system-level cellular adjustments following changes in nutrients availability have been recently described exploiting –omics technologies [5, 6]. These works revealed presence of a deep and systemic re-organization of the overall microbial metabolic network in response to a variation in the composition/concentration of the surrounding nutrients.…”

Section: Introductionmentioning

confidence: 99%

Modelling microbial metabolic rewiring during growth in a complex medium

et al. 2016

View full text Add to dashboard Cite

BackgroundIn their natural environment, bacteria face a wide range of environmental conditions that change over time and that impose continuous rearrangements at all the cellular levels (e.g. gene expression, metabolism). When facing a nutritionally rich environment, for example, microbes first use the preferred compound(s) and only later start metabolizing the other one(s). A systemic re-organization of the overall microbial metabolic network in response to a variation in the composition/concentration of the surrounding nutrients has been suggested, although the range and the entity of such modifications in organisms other than a few model microbes has been scarcely described up to now.ResultsWe used multi-step constraint-based metabolic modelling to simulate the growth in a complex medium over several time steps of the Antarctic model organism Pseudoalteromonas haloplanktis TAC125. As each of these phases is characterized by a specific set of amino acids to be used as carbon and energy source our modelling framework describes the major consequences of nutrients switching at the system level. The model predicts that a deep metabolic reprogramming might be required to achieve optimal biomass production in different stages of growth (different medium composition), with at least half of the cellular metabolic network involved (more than 50% of the metabolic genes). Additionally, we show that our modelling framework is able to capture metabolic functional association and/or common regulatory features of the genes embedded in our reconstruction (e.g. the presence of common regulatory motifs).Finally, to explore the possibility of a sub-optimal biomass objective function (i.e. that cells use resources in alternative metabolic processes at the expense of optimal growth) we have implemented a MOMA-based approach (called nutritional-MOMA) and compared the outcomes with those obtained with Flux Balance Analysis (FBA). Growth simulations under this scenario revealed the deep impact of choosing among alternative objective functions on the resulting predictions of fluxes distribution.ConclusionsHere we provide a time-resolved, systems-level scheme of PhTAC125 metabolic re-wiring as a consequence of carbon source switching in a nutritionally complex medium. Our analyses suggest the presence of a potential efficient metabolic reprogramming machinery to continuously and promptly adapt to this nutritionally changing environment, consistent with adaptation to fast growth in a fairly, but probably inconstant and highly competitive, environment. Also, we show i) how functional partnership and co-regulation features can be predicted by integrating multi-step constraint-based metabolic modelling with fed-batch growth data and ii) that performing simulations under a sub-optimal objective function may lead to different flux distributions in respect to canonical FBA.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3311-0) contains supplementary material, which is available to authorized users.

show abstract

Saccharopolyspora erythraea’sgenome is organised in high-order transcriptional regions mediated by targeted degradation at the metabolic switch

Cited by 31 publications

References 50 publications

A two-component system gene SACE_0101 regulates copper homeostasis in Saccharopolyspora erythraea

A two-component system gene SACE_0101 regulates copper homeostasis in Saccharopolyspora erythraea

Temporal Dynamics of the Saccharopolyspora erythraea Phosphoproteome

Modelling microbial metabolic rewiring during growth in a complex medium

Contact Info

Product

Resources

About